Research Creates the Conditions for Biotech to Generate 1 Billion Doses in Less than a Month – ScienceDaily

By breaking a cell membrane, synthetic biologists at Northwestern University have found a new way to increase the production yield of protein-based vaccines five-fold and significantly expand access to potentially life-saving drugs.

In February, researchers unveiled a new bioproduction platform that enables storage-stable vaccines to be quickly produced at the point of treatment to ensure they are not wasted due to shipping or storage errors. In their new study, the team discovered that enriching cell-free extracts with cell membranes – the components needed to make conjugate vaccines – significantly increased the yields of its freeze-dried platform.

The work creates the conditions to quickly produce drugs at 40,000 doses per liter per day, which cost around $ 1 per dose. At that rate, the team could use a 1,000-liter reactor (about the size of a large garden trash bag) to produce 40 million cans a day, reaching 1 billion cans in less than a month.

“Surely in the time of COVID-19 we all realized the importance of being able to make medicines when and where we need them,” said Michael Jewett of Northwestern, who led the study. “This work will transform the way vaccines are made, including bio-readiness and pandemic response.”

The research will be published April 21 in the journal Nature Communications.

Jewett is Professor of Chemistry and Biotechnology at the McCormick School of Engineering in the Northwest and Director of the Northwestern Center for Synthetic Biology. Jasmine Hershewe and Katherine Warfel, both PhD students in Jewett’s laboratory, are co-first authors of the work.

The new manufacturing platform – called In Vitro Conjugate Vaccine Expression (iVAX) – is made possible by cell-free synthetic biology, in which researchers remove the outer wall (or membrane) of a cell and reuse its internal machinery. The researchers then put this converted machine in a test tube and freeze-dried it. Adding water triggers a chemical reaction that activates the cell-free system, making it a catalyst for making usable drugs when and where they are needed. The platform lasts six months or more, eliminating the need for complicated supply chains and extreme cooling. This makes it a powerful tool for remote or low-resource settings.

In a previous study, Jewett’s team used the iVAX platform to make conjugated vaccines to protect against bacterial infections. At the time, they used Escherichia coli molecular machines to make a vaccine dose in an hour, which cost about $ 5 per dose.

“It was still too expensive and the yields weren’t high enough,” said Jewett. “Our goal was to hit $ 1 a dose, and we met that goal here. By increasing yields and reducing costs, we thought we could potentially provide better access to life-saving drugs.”

Jewett and his team discovered that the key to achieving this goal resides in the cell membrane, which in cell-free synthetic biology is normally discarded. When membranes break apart, they naturally reassemble into vesicles, spherical structures that contain important molecular information. The researchers characterized these vesicles and found that increasing the vesicle concentration could be useful in making components for protein therapeutics such as conjugate vaccines, in which a sugar moiety, unique to a pathogen, is attached to a carrier protein. By learning to recognize this protein as a foreign substance, the body knows how to trigger an immune response to attack it when it is encountered again.

However, attaching this sugar to the carrier protein is a difficult, complex process. The researchers found that the cell membrane contained machines that allowed the sugar to more easily attach to the proteins. By enriching vaccine extracts with this membrane-bound machinery, the researchers were able to significantly increase the yields of usable vaccine doses.

“Nearly 30% of the genome is used to encode membrane proteins for a wide variety of organisms,” said study co-author Neha Kamat, an assistant professor of biomedical engineering at McCormick and an expert on cell membranes. “Membrane proteins are a really important part of life. By learning how to use membrane proteins effectively, we can really evolve cell-free systems.”

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Materials provided by Northwestern University. Originally written by Amanda Morris. Note: The content can be edited by style and length.